The anterior pituitary hormone prolactin (PRL) is encoded by a member of the growth hormone/prolactin/placental lactogen gene family. In mammals, it is primarily responsible for the development of the mammary gland and lactation. Prolactin stimulates the expression of milk protein genes by increasing both gene transcription and mRNA half-like.
In addition to the classical effects in the mammary gland, prolactin has been shown to have a number of other actions, all of which are initiated by an interaction with specific high affinity receptors located on the plasma membrane and widely distributed in a number of tissues.
Different biological approaches (cross-linking, immunoprecipitation, or immunoblot with monoclonal antibodies) have shown that the prolactin receptor in many tissues has a relative molecular mass (M.sub.r) of approximately 40,000 and is apparently not linked by disulfide bonds to itself or to other subunits. There are reports of larger (70,000-80,000) molecular weight forms of the receptor.
Prolactin receptor levels are differentially regulated depending on the tissue studied. In rat liver, for example, one of the tissues with the highest prolactin binding, receptor levels vary during the estrous cycle, increase during pregnacy, and are markedly stimulated by estrogens. Prolactin plays a major role in the regulation of its own receptor, inducing both up- and down-regulation depending on the concentration and duration of exposure to prolactin.
However, as is true for grown hormone (GH), no means of signal transduction has been identified for prolactin. There are no clear effects of prolactin on cyclic AMP, cyclic GMP, inositol phospholipids, phosphorylation, calcium ions, or ion channels. Neither the GH nor the PRL receptor appear to be a tyrosine kinase.
A better understanding of prolactin receptor structure, regions involved in hormone binding, signal transduction, and possible homology with other hormone receptors would certainly help to shed some light on the mechanism by which prolactin induces its various actions.
Recently, the amino acid sequences of the rabbit and human GH receptors were deduced from their respective cDNA sequences. The authors found no sequence homology of the GH receptor with any other reported protein. Furthermore, the rat PRL receptor was recently purified by Boutin et al. as described in 1988 Cell Vol. 53, 69-77, who also obtained partial amino acid sequence information and cloned and sequence the cDNA. Comparison of the sequence with that of the mammalian growth hormone receptor demonstrated some regions of identity between the two receptors, suggesting the receptors originated from a common ancestor.
It is well known that prolactin plays a major role in the development of the mammary gland and in the induction and maintenance of lactation, via a stimulation of the expression of milk protein genes. The measurement of prolactin receptor levels may be used as a means of predicting the response of a patient with breast cancer, since tumors containing prolactin receptors may be more differentiated and thus less progressed toward a cancerous state. Therefore, the isolation and sequencing of the cDNA and gene encoding the production of human prolactin receptor, as well as its expression in cell lines, would be highly desirable.